Fetal growth restriction (FGR) is a major contributor to perinatal mortality and morbidity worldwide. The hypothesis for the proposed study is that mal-development of the placental microvasculature and its negative regulation by environmental influences such smoking elicit FGR. Our specific aims are a) Determine how placental villous structure, vascularization and blood flow predict FGR and associated adverse pregnancy outcomes using a novel technology, superb microvascular imaging (SMI); b) Visualize in situ spiral artery transformation in normal pregnancies and investigate how spiral artery transformation contributes to FGR using SMI and c) Validate SMI, Doppler and MRI findings at the cellular and molecular levels in FGR complicated vs. normal pregnancies. We utilize both prospective and nested case-control study designs to investigate placental microvasculature assessed using SMI technology and estimate the influence of smoking on the indices and their association with FGR. The primary outcome will be FGR. Relevance: Fetal growth restriction affects approximately 10% of pregnancies and is a significant contributor to perinatal death. Attempts at predicting pregnancies at risk for this complications has been disappointing. This proposal will fill that void by using an approach incorporating multiple parameters in designing a reliable prediction model for these complications.